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Steroid hormones control circadian Elovl3 expression in mouse liver
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2008 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 149, no 6, 3158-3166 p.Article in journal (Refereed) Published
Abstract [en]

The Elovl3 gene belongs to the Elovl gene family, which encodes for enzymes involved in the elongation of very long chain fatty acids. The recognized role for the enzyme is to control the elongation of saturated and monounsaturated fatty acids up to 24 carbons in length. Elovl3 was originally identified as a highly expressed gene in brown adipose tissue on cold exposure. Here we show that hepatic Elovl3 mRNA expression follows a distinct diurnal rhythm exclusively in mature male mice, with a sharp increase early in the morning Zeitgeber time (ZT) 20, peaks around ZT2, and is back to basal level at the end of the light period at ZT10. In female mice and sexually immature male mice, the Elovl3 expression was constantly low. Fasting and refeeding mice with chow or high-fat diet did not alter the Elovl3 mRNA levels. However, animals that were exclusively fed during the day for 9 d displayed an inverted expression profile. In addition, we show that Elovl3 expression is transcriptionally controlled and significantly induced by the exposure of the synthetic glucocorticoid dexamethasone. Taken together, these data suggest that Elovl3 expression in mouse liver is under strict diurnal control by circulating steroid hormones such as glucocorticoids and androgens. Finally, Elovl3 expression was found to be elevated in peroxisomal transporter ATP-binding cassette, subfamily D(ALD), member 2 ablated mice and suppressed in ATP-binding cassette subfamily D(ALD) member 2 overexpressing mice, implying a tight cross talk between very long chain fatty acid synthesis and peroxisomal fatty acid oxidation

Place, publisher, year, edition, pages
2008. Vol. 149, no 6, 3158-3166 p.
Keyword [en]
Androgens/*pharmacology, Animals, Circadian Rhythm/*physiology, Gene Expression Profiling, Gene Expression Regulation, Glucocorticoids/*pharmacology, Liver/drug effects/*metabolism, Male, Membrane Proteins/drug effects/*genetics, Mice, Mice; Inbred Strains, PPAR alpha/pharmacology, Transcription; Genetic
National Category
Biological Sciences
URN: urn:nbn:se:su:diva-25706DOI: 10.1210/en.2007-1402ISI: 000256053100054OAI: diva2:200320
Part of urn:nbn:se:su:diva-8469Available from: 2009-02-05 Created: 2009-01-28 Last updated: 2012-03-08Bibliographically approved
In thesis
1. Regulation of Elovl and fatty acid metabolism
Open this publication in new window or tab >>Regulation of Elovl and fatty acid metabolism
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fatty acids are important regulators in the control of mammalian energy homeostasis. They are ingested in the diet but a significant amount are also endogenously produced by de novo lipogenesis. Fatty acid elongation beyond 16 carbons (palmitic acid) can occur to generate very long chain fatty acids (VLCFA), a process that is initiated by the rate-limiting condensation reaction. To date, six mammalian enzymes responsible for this reaction, ELOVL1-6 (Elongation of very long chain fatty acid), have been characterized. All of them exert substrate specificity and tissue-specific gene expression. In this thesis, factors that regulate fatty acid metabolism and, in particular, fatty acid synthesis and elongation will be presented.

The enclosed papers discuss issues as to how Elovl3 is regulated in liver and in different adipose depots and what effects ablation of this enzyme causes to lipid homeostasis. Hepatic Elovl3 gene expression followed a circadian rhythm, present exclusively in sexually mature male mice. In contrast to the expression of several other lipogenic genes, Elovl3 gene expression was not affected by fasting or refeeding. Instead, the gene expression was influenced by steroid hormones such as glucocorticoids and sex hormones.

Interestingly, despite reduced levels of leptin, Elovl3-ablated mice were shown to be resistant to diet induced weight gain, which seemed to be due to a decreased ratio between energy intake and energy expenditure. This phenotype was more pronounced in female mice.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2009. 58 p.
fatty acid metabolism, fatty acid elongation
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Research subject
urn:nbn:se:su:diva-8469 (URN)978-91-7155-798-8 (ISBN)
Public defence
2009-02-27, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.Available from: 2009-02-05 Created: 2009-01-28 Last updated: 2011-02-23Bibliographically approved

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